Field
The invention is generally directed to compositions, systems and methods for detecting one or more species of polypeptide in a complex mixture of polypeptides and polypeptide complexes. Specifically, the invention includes compositions, systems and methods for detecting homodimers in a mixture of multimers that include bispecific antibodies.
Related Art
Monoclonal antibodies represent an important class of therapeutics for various diseases. There is a growing interest in increasing the versatility of monoclonal antibodies, with one approach being the design and generation of bispecific antibodies (bsAb). Conventional expression of a bsAb using two heavy and two light chains will result in multiple (up to ten) undesirable multimeric protein products due to the random association of heavy and light chains. Co-expression of two unique heavy chains and one common light chain will minimize the number of side products to two homodimeric species, which may need to be subsequently removed during purification. Thus, a need for effective and efficient methods to detect and differentiate homodimer side products from the desired heterodimer (bsAb) exists. Reagents and methods to estimate the purity of a bsAb consisting of two unique heavy chains and two identical light chains are disclosed.